Neurological and epidemiological aspects of a BoHV-5 meningoencephalitis outbreak

Bovine herpesvirus 5 is a DNA virus that has been associated with meningoencephalitis in young cattle. While its clinical diagnosis is obscured by other major diseases that also produce similar neurological disease in cattle, the use of conventional virological techniques is hampered by the establishment of a lifelong latent infection in the host and the difficulty in differentiating BoHV-1 and BoHV-5. The aim of the current report is to describe the clinical and epidemiological aspects observed in a natural outbreak of BoHV-5 meningoencephalitis in a dairy cattle herd from Brazil. In the outbreak, the affected animals consisted of nine calves, which presented three possible forms of the neurological disease, subjectively classified as peracute, acute, and subacute/chronic. In contrast to conventional herpetic meningoencephalitis, characterized mainly by progressive multifocal brain dysfunctions, BoHV-5 infection resulted in focal non-progressive caudal brainstem dysfunction (pontomedullary syndrome) in an animal presented with subacute/chronic BoHV-5 meningoencephalitis. The evaluation of CNS tissue of affected calves through both histological examination and multiplex-PCR was able to confirm BoHV-5 infection. Additionally, the analysis of CSF samples through PCR allowed ante-mortem BoHV-5 diagnosis during the outbreak, which enabled the implementation of several measures of control for the disease.

Download Full-text

Bovine herpesvirus 5 detection by virus isolation in cell culture and multiplex-PCR in central nervous system from cattle with neurological disease in Brazilian herds

Brazilian Journal of Microbiology ◽

10.1590/s1517-83822007000300019 ◽

2007 ◽

Vol 38 (3) ◽

pp. 485-490 ◽

Cited By ~ 9

Author(s):

Marlise Pompeo Claus ◽

Alice Fernandes Alfieri ◽

Kerlei Cristina Médici ◽

Michele Lunardi ◽

Amauri Alcindo Alfieri

Keyword(s):

Central Nervous System ◽

Cell Culture ◽

Nervous System ◽

Multiplex Pcr ◽

Neurological Disease ◽

Virus Isolation ◽

Bovine Herpesvirus

Download Full-text

Latent infection by bovine herpesvirus type-5 in experimentally infected rabbits: virus reactivation, shedding and recrudescence of neurological disease

Veterinary Microbiology ◽

10.1016/s0378-1135(01)00441-2 ◽

2002 ◽

Vol 84 (4) ◽

pp. 285-295 ◽

Cited By ~ 24

Author(s):

L Caron ◽

E.F Flores ◽

R Weiblen ◽

C.F.C Scherer ◽

L.F Irigoyen ◽

...

Keyword(s):

Neurological Disease ◽

Latent Infection ◽

Bovine Herpesvirus ◽

Virus Reactivation ◽

Herpesvirus Type ◽

Bovine Herpesvirus Type 5

Download Full-text

Intrapreputial infection of young bulls with bovine herpesvirus type 1.2 (BHV-1.2): acute balanoposthitis, latent infection and detection of viral DNA in regional neural and non-neural tissues 50 days after experimental reactivation

Veterinary Microbiology ◽

10.1016/j.vetmic.2003.09.020 ◽

2004 ◽

Vol 98 (3-4) ◽

pp. 185-196 ◽

Cited By ~ 17

Author(s):

F.S.F Vogel ◽

E.F Flores ◽

R Weiblen ◽

E.R Winkelmann ◽

M.P Moraes ◽

...

Keyword(s):

Latent Infection ◽

Bovine Herpesvirus ◽

Viral Dna ◽

Herpesvirus Type ◽

Neural Tissues

Download Full-text

Experimental infection of rabbits with a recombinant bovine herpesvirus type 5 (BoHV-5) gI, gE and US9-negative

Pesquisa Veterinária Brasileira ◽

10.1590/s0100-736x2009001100009 ◽

2009 ◽

Vol 29 (11) ◽

pp. 913-918 ◽

Cited By ~ 1

Author(s):

Alessandra D'Avila Silva ◽

Ana Cláudia Franco ◽

Paulo Augusto Esteves ◽

Fernando Rosado Spilki ◽

Paulo Michel Roehe

Keyword(s):

Neurological Disease ◽

Age Groups ◽

Clinical Signs ◽

Bovine Herpesvirus ◽

Wild Type ◽

Herpesvirus Type ◽

Viral Genes ◽

Bovine Herpesvirus Type 5 ◽

Two Age Groups

Bovine herpesvirus type 5 (BoHV-5) is a major cause of viral meningoencephalitis in cattle. The expression of different viral proteins has been associated with BoHV-5 neuropathogenesis. Among these, gI, gE and US9 have been considered essential for the production of neurological disease in infected animals. To evaluate the role of gI, gE and US9 in neurovirulence, a recombinant from which the respective genes were deleted (BoHV-5 gI-/gE-/US9-) was constructed and inoculated in rabbits of two age groups (four and eight weeks-old). When the recombinant virus was inoculated through the paranasal sinuses of four weeks-old rabbits, neurological disease was observed and death was the outcome in 4 out of 13 (30.7 %) animals, whereas clinical signs and death were observed in 11/13 (84.6%) of rabbits infected with the parental virus. In eight weeks-old rabbits, the BoHV-5 gI-/gE-/US9- did not induce clinically apparent disease and could not be reactivated after dexamethasone administration, whereas wild type BoHV-5 caused disease in 55.5% of the animals and was reactivated. These findings reveal that the simultaneous deletion of gI, gE and US9 genes did reduce but did not completely abolish the neurovirulence of BoHV-5 in rabbits, indicating that other viral genes may also play a role in the induction of neurological disease.

Download Full-text

Equine herpesviruses: a roundtable discussion

UK-Vet Equine ◽

10.12968/ukve.2019.3.s2.1 ◽

2019 ◽

Vol 3 (Sup4) ◽

pp. 1-12 ◽

Cited By ~ 1

Author(s):

Philip Ivens ◽

David Rendle ◽

Julia Kydd ◽

James Crabtree ◽

Sarah Moore ◽

...

Keyword(s):

Neurological Disease ◽

Latent Infection ◽

Domestic Horse ◽

Respiratory Pathogens ◽

Roundtable Discussion ◽

Virus Shedding ◽

Demographic Groups ◽

Clinical Pathogens ◽

Equine Herpesviruses ◽

Horse Owners

Foreword There are nine different equid herpesviruses (EHVs). Five types (EHV-1 to EHV-5) infect the domestic horse, while EHV-6 to EHV-9 are associated with infections in wild equids including asses and zebra. This review focuses on the commonest and most important clinical pathogens, the alphaherpesviruses EHV-1 and 4. These are respiratory pathogens and are also responsible for abortion and neurological disease. Several aspects of the biology of these viruses makes their control challenging. In particular, latent infection and reactivation of infection under stress, with subsequent virus shedding, makes elimination of these viruses impossible. Biosecurity measures are important both for minimising the risk of an outbreak and for controlling any outbreak when it occurs. Recognition of the disease and confirmatory diagnosis are also important in order for appropriate biosecurity measures to be instigated. Vaccination in key demographic groups is also important to reduce severe clinical disease. Unfortunately many horse owners are unaware of EHV or the importance of biosecurity measures and vaccination for control.

Download Full-text

Immunity to Bovine Herpesvirus 1: I. Viral lifecycle and innate immunity

Animal Health Research Reviews ◽

10.1017/s1466252313000042 ◽

2013 ◽

Vol 14 (1) ◽

pp. 88-102 ◽

Cited By ~ 17

Author(s):

Randall L. Levings ◽

James A. Roth

Keyword(s):

Immune Response ◽

Latent Infection ◽

Bovine Herpesvirus ◽

Lytic Replication ◽

Host Cells ◽

Type I Interferons ◽

Disease Spread ◽

Type I ◽

Bovine Herpesvirus 1 ◽

Herpesvirus 1

AbstractBovine herpesvirus 1 (BHV-1) causes a variety of diseases and is globally distributed. It infects via mucosal epithelium, leading to rapid lytic replication and latent infection, primarily in sensory ganglia. Large amounts of virus can be excreted by the host on primary infection or upon recrudescence of latent infection, resulting in disease spread. The bovine immune response to BHV-1 is rapid, robust, balanced, and long-lasting. The innate immune system is the first to respond to the infection, with type I interferons (IFNs), inflammatory cytokines, killing of infected host cells, and priming of a balanced adaptive immune response. The virus possesses a variety of immune evasion strategies, including inhibition of type I IFN production, chemokine and complement binding, infection of macrophages and neutrophils, and latency. BHV-1 immune suppression contributes to the severity of its disease manifestations and to the bovine respiratory disease complex, the leading cause of cattle death loss in the USA.

Download Full-text

Infections of Calves with Antigenic Variants of Bovine Herpesvirus 1 (BHV-1) and Neurological Disease

Journal of Veterinary Medicine Series B ◽

10.1111/j.1439-0450.1986.tb00036.x ◽

1986 ◽

Vol 33 (1-10) ◽

pp. 303-310 ◽

Cited By ~ 39

Author(s):

A. A. Schudel ◽

B. J. Carrillo ◽

R. Wyler ◽

A. E. Metzler

Keyword(s):

Neurological Disease ◽

Bovine Herpesvirus ◽

Bovine Herpesvirus 1 ◽

Herpesvirus 1

Download Full-text

A thymidine kinase-negative bovine herpesvirus 5 is highly attenuated for rabbits, but is neuroinvasive and establishes latent infection

Pesquisa Veterinária Brasileira ◽

10.1590/s0100-736x2011000500005 ◽

2011 ◽

Vol 31 (5) ◽

pp. 389-397

Author(s):

Sara Campos da Silva ◽

Mário Celso Speroto Brum ◽

Stephan A.M. de Oliveira ◽

Rudi Weiblen ◽

Eduardo F Flores

Keyword(s):

Thymidine Kinase ◽

Recombinant Virus ◽

Molecular Mechanisms ◽

Latent Infection ◽

Bovine Herpesvirus ◽

Parental Virus ◽

Specific Gene ◽

High Dose ◽

Nasal Secretions ◽

The Brain

Mutant viral strains deleted in non-essential genes represent useful tools to study the function of specific gene products in the biology of the virus. We herein describe an investigation on the phenotype of a bovine herpesvirus 5 (BoHV-5) recombinant deleted in the gene encoding the enzyme thymidine kinase (TK) in rabbits, with special emphasis to neuroinvasiveness and the ability to establish and reactivate latent infection. Rabbits inoculated with the parental virus (SV-507/99) (n=18) at a low titer (10(5.5)TCID50) shed virus in nasal secretions in titers up to 10(4.5)TCID50 for up to 12 days (average: 9.8 days [5-12]) and 5/ 16 developed neurological disease and were euthanized in extremis. Rabbits inoculated with the recombinant BoHV-5TKΔ at a high dose (10(7.1)TCID50) also shed virus in nasal secretions, yet to lower titers (maximum: 10(2.3)TCID50) and for a shorter period (average: 6.6 days [2-11]) and remained healthy. PCR examination of brain sections of inoculated rabbits at day 6 post-infection (pi) revealed a widespread distribution of the parental virus, whereas DNA of the recombinant BoHV-5TKΔ-was detected only in the trigeminal ganglia [TG] and olfactory bulbs [OB]. Nevertheless, during latent infection (52pi), DNA of the recombinant virus was detected in the TGs, OBs and also in other areas of the brain, demonstrating the ability of the virus to invade the brain. Dexamethasone (Dx) administration at day 65 pi was followed by virus reactivation and shedding by 5/8 rabbits inoculated with the parental strain (mean duration of 4.2 days [1 - 9]) and by none of seven rabbits inoculated with the recombinant virus. Again, PCR examination at day 30 post-Dx treatment revealed the presence of latent DNA in the TGs, OBs and in other areas of the brain of both groups. Taken together, these results confirm that the recombinant BoHV-5TKΔ is highly attenuated for rabbits. It shows a reduced ability to replicate in the nose but retains the ability to invade the brain and to establish latent infection. Additional studies are underway to determine the biological and molecular mechanisms underlying the inability of BoHV-5TKΔ to reactivate from latency.

Download Full-text

Mapping the sites of latency and reactivation by bovine herpesvirus 5 (BoHV-5) and a thymidine kinase-deleted BoHV-5 in lambs

Pesquisa Veterinária Brasileira ◽

10.1590/s0100-736x2013001200003 ◽

2013 ◽

Vol 33 (12) ◽

pp. 1403-1415

Author(s):

Gustavo C. Cadore ◽

Gian Marcon ◽

Mario Celso Sperotto Brum ◽

Rudi Weiblen ◽

Eduardo F. Flores

Keyword(s):

Thymidine Kinase ◽

Recombinant Virus ◽

Latent Infection ◽

Bovine Herpesvirus ◽

Vaccine Safety ◽

Parental Virus ◽

Lymphoid Tissues ◽

Post Inoculation ◽

Sheep Model ◽

Reverse Transcription Pcr

A thymidine kinase (tk)-deleted bovine herpesvirus 5 (BoHV-5tkΔ) was previously shown to establish latent infection and reactivate - even poorly - in a sheep model (Cadore et al. 2013). As TK-negative alphaherpesviruses are unlike to reactivate in neural tissue, this study investigated the sites of latency and reactivation by this recombinant in lambs. For this, groups of lambs were inoculated intranasally with the parental BoHV-5 strain (SV-507/99) or with the recombinant BoHV-5tkΔ. During latent infection (40 days post-inoculation, pi), the distribution of recombinant virus DNA in neural and non-neural tissues was similar to that of the parental virus. Parental and recombinant virus DNA was consistently detected by PCR in trigeminal ganglia (TGs); frequently in palatine and pharyngeal tonsils and, less frequently in the retropharyngeal lymph nodes. In addition, latent DNA of both viruses was detected in several areas of the brain. After dexamethasone (Dx) administration (day 40pi), the recombinant virus was barely detected in nasal secretions contrasting with marked shedding of the parental virus. In tissues of lambs euthanized at day 3 post-Dx treatment (pDx), reverse-transcription-PCR (RT-PCR) for a late viral mRNA (glycoprotein D gene) demonstrated reactivation of parental virus in neural (TGs) and lymphoid tissues (tonsils, lymph node). In contrast, recombinant virus mRNA was detected only in lymphoid tissues. These results demonstrate that BoHV-5 and the recombinant BoHV-5tkΔ do establish latent infection in neural and non-neural sites. Reactivation of the recombinant BoHV-5tkΔ, however, appeared to occur only in non-neural sites. In anyway, the ability of a tk-deleted strain to reactivate latent infection deserves attention in the context of vaccine safety.

Download Full-text